Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) is considered to be a major regulator of angiogenesis in various brain tumors. In this study, we determined the expression levels of VEGF, and vascular endothelial growth factor receptor (VEGFR)-1 and -2 mRNA in 46 intracranial schwannomas by quantitative real-time PCR, and correlated these with various clinical factors or other molecular markers. We found that these tumors expressed significant amounts of VEGF mRNA in comparison with other brain tumors, including malignant gliomas and meningiomas. In addition, we performed immunohistochemical studies for VEGF and VEGFR-1, and confirmed that these tumors prominently express these proteins. The expression levels of VEGF and VEGFR-1 mRNA in recurrent tumors were higher than those in primary tumors. When we divided patients into two groups according to VEGF mRNA expression in the tumor, there was no significant difference in patient age, gender, or cranial nerves of origin between groups; however, the tumor volume tended to be larger in the high VEGF group than in the low VEGF group. The levels of VEGFR-1 mRNA and neurofibromatosis-2 mRNA in the high VEGF group were significantly greater than those in the low VEGF group. Levels of VEGFR-2 mRNA and DNA topoisomerase IIalpha mRNA, and the MIB-1 labeling index in the high VEGF group were slightly higher than those in the low VEGF group; however, the difference was not statistically significant. Based on these observations, the significance of VEGF and its receptor genes in intracranial schwannomas is discussed.
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PMID:Expression of VEGF and its receptor genes in intracranial schwannomas. 1757 36

Equilibrative nucleoside transporter 1 (ENT1) is a major regulator for the uptake of [(18)F]fluorothymidine ([(18)F]FLT), a promising positron emission tomography tracer for treatment monitoring. Various antimetabolites such as 5-fluorouracil often increase ENT1 activity and [(18)F]FLT uptake (flare) in spite of cell death. However, it has not yet been defined which agents induce [(18)F]FLT flare and what is the role of [(18)F]FLT flare in cell viability. Sixty cytotoxic agents from the LOPAC1280 library were screened for ENT1 activity in HeLa cells which predominantly express ENT1, and topoisomerase inhibitors (i.e., aurintricarboxylic acid, idarubicin, camptothecin and etoposide) were identified as potent inducers of ENT1 activity. The changes in ENT1 activity were closely correlated with [(3)H]FLT uptake (Spearman's correlation coefficient, r=0.66; P<0.01). Etoposide significantly increased ENT1 activity and [(3)H]FLT uptake accompanying cell cycle arrest at S/G2/M phase and the increase in TK1 expression and activity in both ENT1-low expressing HT29 and ENT1-high expressing MDA-MB-231 cells. The inhibition of ENT1 activity by dipyridamol or S-(p-nitrobenzyl)-6-thioinosine repressed the etoposide-induced cell death in HeLa cells, whereas it induced no changes in the other cell lines. In conclusion, etoposide is identified as a potent inducer for ENT1 activity and [(3)H]FLT uptake. The role of ENT1 activity by etoposide was cell-type dependent, which requests caution for the application of ENT1-mediated [(18)F]FLT flare for treatment monitoring.
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PMID:Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: screening of 60 cytotoxic agents. 2323 55